CXCL1 as a novel prognostic biomarker and immune regulator in colon adenocarcinoma

Colon Adenocarcinoma (COAD) remains a prominent problem among cancers today. COAD is one of the malignancies with a significant overexpression of CXCL1, an enzyme involved in cellular metabolism. However, the key targets for colon cancer are not yet well understood. As a result, the purpose of this study is to examine the mechanism of CXCL1 in order to assess its potential as a predictive biomarker for colon cancer. Genetic changes, genomic expression, and methylation analyses were sourced from the TCGA, CPTAC, UALCAN, HPA, cBioPortal, and MethSurv databases. The gene expression is validated by qPCR. The diagnostic and prognostic significance of CXCL1 in COAD was assessed using data from ROC analysis and KM-plotter. Functional analyses were performed utilizing the GeneMANIA and STRING databases, along with gene-gene and PPI networks, GO terms, and KEGG pathway analyses. The relationship with immune escape was explored through analyses conducted using the TIMER, TISIDB, and GEPIA databases. Additionally, GSCALite was utilized to analyze drug sensitivity in relation to CXCL1 expression in tumors. CXCL1 expression was found to be statistically significantly higher in COAD cells than in their corresponding normal control cells, according to qPCR analysis. ROC analysis identified CXCL1 as a highly accurate biomarker for diagnosing COAD (AUC = 0.725). Univariate Cox regression and KM analysis indicated that while high CXCL1 expression was significantly associated with improved OS and RFS (P < 0.001), its genetic alteration (amplification) was associated with a significantly shorter DFI (P = 0.037). Functional analyses confirmed CXCL1’s role in chemokine-mediated signaling and leukocyte chemotaxis, and also suggested involvement in cellular redox metabolism. Furthermore, CXCL1 overexpression was strongly correlated with promoter hypomethylation (e.g., cg19170015, P < 6e-10), and this hypomethylation intensified with advancing pathological stage. CXCL1 expression exhibited a robust correlation with the infiltration of myeloid cells, particularly macrophage (Rho = 0.693) and neutrophil cells, strongly suggesting it affects the TME and is associated with immune checkpoints. Finally, high CXCL1 expression was broadly correlated with drug resistance in pan-cancer cell lines but showed mixed sensitivity associations in COAD-specific cell lines. This study’s comprehensive analyses indicate CXCL1 as a novel biomarker for COAD.